AJP - Renal Physiology, Vol 259, Issue 4 539-F544, Copyright © 1990 by American Physiological Society
Stimulation of renin secretion by ethacrynic acid is independent of Na(+)-K(+)-2Cl- cotransport
C. S. Park, P. S. Doh, R. E. Carraway, G. G. Chung, J. C. Fray and T. B. Miller
Department of Physiology, University of Massachusetts Medical School, Worcester 01655.
This study investigated the cellular mechanism of stimulation of renin
secretion by the loop diuretic ethacrynic acid (EA) in rabbit renal
cortical slices. The diuretic rapidly stimulated renin secretion reversibly
and in a concentration-dependent manner. The stimulation was independent of
the presence of Na+, Cl-, Ca2+, or other loop diuretics (furosemide and
bumetanide) in the incubation media, suggesting that the stimulation in
vitro was not dependent on the inhibitory effect of the diuretic on
Na(+)-K(+)-2Cl-cotransport. The findings do not support the macula densa
hypothesis. The stimulation by the diuretic was prevented and reversed by
thiols such as cysteine and dithiothreitol, which also prevented and
reversed the stimulation of renin secretion by the nondiuretic sulfhydryl
reagent P-chloromercuriphenyl-sulfonate (PCMPS). These results suggest that
EA stimulates renin secretion in vitro via reversible chemical reactions
with specific membrane sulfhydryl groups that may have no functional role
in the Na(+)-K(+)-2Cl- cotransport.
